[Meteorological Influences on Annual Variation and Trend of Autumn Surface Ozone in the Pearl River Delta].

Based on the ozone （O3） monitoring data of the Pearl River Delta （PRD） from 2015 to 2022 and the reanalysis of meteorological data, the impact of meteorological conditions on the annual variation and trends of the maximum daily 8-hour average O3 concentration （MDA8-O3） were quantified using multiple linear regression （MLR） and LMG methods. The results indicated that the MLR model constructed using meteorological parameters from individual months in autumn better simulated the variation in MDA8-O3 compared to that in the model built using meteorological parameters from the entire autumn season. The combined influence of total cloud cover, relative humidity, 2 m maximum temperature, and 850 hPa zonal wind led to a reduction of 34.1 µg·m-3 in MAD8-O3 in 2020 compared to that in 2019, with contributions of 31.3%, 45.2%, 15.8%, and 6.7%, respectively. The observed trends of MDA8-O3 in the PRD for September, October, November, and the autumn season during 2015-2022 were 7.3, 5.2, 4.8, and 5.8 µg·ï¼ˆm3·a）-1, respectively. Among these, the trends driven by meteorological factors were 3.6, 2.4, 2.4, and 3.1 µg·ï¼ˆm3·a）-1. Overall, meteorological conditions contributed 53.4% to the variations in autumn MDA8-O3 in the PRD from 2015 to 2022.

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Halotolerant Bacillus sp. strain RA coordinates myo-inositol metabolism to confer salt tolerance to tomato.

Soil salinity is a worldwide problem threatening crop yields. Some plant growth-promoting rhizobacteria (PGPR) could survive in high salt environment and assist plant adaptation to stress. Nevertheless, the genomic and metabolic features, as well as the regulatory mechanisms promoting salt tolerance in plants by these bacteria remain largely unknown. In the current work, a novel halotolerant PGPR strain, namely, Bacillus sp. strain RA can enhance tomato tolerance to salt stress. Comparative genomic analysis of strain RA with its closely related species indicated a high level of evolutionary plasticity exhibited by strain-specific genes and evolutionary constraints driven by purifying selection, which facilitated its genomic adaptation to salt-affected soils. The transcriptome further showed that strain RA could tolerate salt stress by balancing energy metabolism via the reprogramming of biosynthetic pathways. Plants exude a plethora of metabolites that can strongly influence plant fitness. The accumulation of myo-inositol in leaves under salt stress was observed, leading to the promotion of plant growth triggered by Bacillus sp. strain RA. Importantly, myo-inositol serves as a selective force in the assembly of the phyllosphere microbiome and the recruitment of plant-beneficial species. It promotes destabilizing properties in phyllosphere bacterial co-occurrence networks, but not in fungal networks. Furthermore, interdomain interactions between bacteria and fungi were strengthened by myo-inositol in response to salt stress. This work highlights the genetic adaptation of RA to salt-affected soils and its ability to impact phyllosphere microorganisms through the adjustment of myo-inositol metabolites, thereby imparting enduring resistance against salt stress in tomato.

An adult with hemorrhagic varicella co-infects with cytomegalovirus: a case report.

BACKGROUND: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. CASE PRESENTATION: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella. CONCLUSION: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.

Review of the genus Paradelius De Saeger, 1942 of East Asia (Hymenoptera, Braconidae, Cheloninae, Adeliini) with the description of a new species from South Korea.

The East Palaearctic species of the adeliine genus Paradelius De Saeger, 1942 are reviewed. The genus Sculptomyriola Belokobylskij, 1988 is synonymised with Paradelius and treated as its subgenus. The following species are transferred to subgenus Paradelius (Sculptomyriola): P. (Sc.) extremiorientalis (Belokobylskij, 1988), comb. nov.; P. (Sc.) ghilarovi (Belokobylskij, 1988), comb. nov.; P. (Sc.) neotropicalis Shimbori & Shaw, 2019; P. (Sc.) nigrus Whitfield, 1988; P. (Sc.) rubrus Whitfield, 1988; P. (Sc.) sinevi (Belokobylskij, 1998), comb. nov. A new species Paradelius (Sculptomyriola) koreanussp. nov. from Korean Peninsula is described. The genus Sinadelius He & Chen, 2000 is synonymised with Paradelius De Saeger and also treated as its subgenus. The species Sinadeliusguangxiensis He & Chen, 2000 and S.nigricans He & Chen, 2000 are transferred to Paradelius (Sinadelius) (comb. nov.). A key for determination of the World known Paradelius species from three its subgenera, Paradelius s.str., Sculptomyriola Belokobylskij and Sinadelius He & Chen, and illustrated redescriptions of the type of genus and its Asian species are provided.

Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade.

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.

HSP90ß shapes the fate of Th17 cells with the help of glycolysis-controlled methylation modification.

BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the ß but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90ß would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms. EXPERIMENTAL APPROACH: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90ß. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms. KEY RESULTS: The selective pharmacological inhibitor (HSP90ßi) and shHSP90ß significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically-transformed Th17 cells by HSP90ßi or shHSP90ß were able to inhibit lymphocyte proliferation and colitis in mice. HSP90ßi and shHSP90ß selectively weakened glycolysis by stopping the direct association of HSP90ß and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate-STAT5-TET2" cascade. CONCLUSION AND IMPLICATIONS: HSP90ß shapes the fate of Th17 cells via glycolysis-controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC.

The influence of the number of tree searches on maximum likelihood inference in phylogenomics.

Maximum likelihood (ML) phylogenetic inference is widely used in phylogenomics. As heuristic searches most likely find suboptimal trees, it is recommended to conduct multiple (e.g., ten) tree searches in phylogenetic analyses. However, beyond its positive role, how and to what extent multiple tree searches aid ML phylogenetic inference remains poorly explored. Here, we found that a random starting tree was not as effective as the BioNJ and parsimony starting trees in inferring ML gene tree and that RAxML-NG and PhyML were less sensitive to different starting trees than IQ-TREE. We then examined the effect of the number of tree searches on ML tree inference with IQ-TREE and RAxML-NG, by running 100 tree searches on 19,414 gene alignments from 15 animal, plant, and fungal phylogenomic datasets. We found that the number of tree searches substantially impacted the recovery of the best-of-100 ML gene tree topology among 100 searches for a given ML program. In addition, all of the concatenation-based trees were topologically identical if the number of tree searches was ≥ 10. Quartet-based ASTRAL trees inferred from 1 to 80 tree searches differed topologically from those inferred from 100 tree searches for 6 /15 phylogenomic datasets. Lastly, our simulations showed that gene alignments with lower difficulty scores had a higher chance of finding the best-of-100 gene tree topology and were more likely to yield the correct trees.

Robust variability of grid cell properties within individual grid modules enhances encoding of local space.

Although grid cells are one of the most well studied functional classes of neurons in the mammalian brain, the assumption that there is a single grid orientation and spacing per grid module has not been carefully tested. We investigate and analyze a recent large-scale recording of medial entorhinal cortex to characterize the presence and degree of heterogeneity of grid properties within individual modules. We find evidence for small, but robust, variability and hypothesize that this property of the grid code could enhance the ability of encoding local spatial information. Performing analysis on synthetic populations of grid cells, where we have complete control over the amount heterogeneity in grid properties, we demonstrate that variability, of a similar magnitude to the analyzed data, leads to significantly decreased decoding error, even when restricted to activity from a single module. Our results highlight how the heterogeneity of the neural response properties may benefit coding and opens new directions for theoretical and experimental analysis of grid cells.

Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes.

Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.

Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family members.

Acute myeloid leukemia (AML) remains challenging due to chemotherapeutic drug-resistance (CDR). Aberrant expression B7 family proteins are involved in tumors evasion. We wonder whether B7 family protein alteration in AML CDR further supports tumor escape. Here, we establish AML cytarabine-resistant cell line U937/Ara-C and report on the expression MHC molecule and B7 family member. HLA-ABC was highly expressed similarly on both cell lines. MIC (MHC class I chain related) A/B and B7-H6 was moderately expressed on the surface of U937 and decreased dramatically by U937/Ara-C. In contrast, enhanced expression of B7-H1 and B7-H7 by U937/Ara-C was observed. HLA-DR and other B7 family members including CD80, CD86, B7-DC, B7-H2, B7-H3, B7-H4, and B7-H5 were not detected by both cell lines. Compared co-cultured with U937, peripheral blood mononuclear cells showed a decreased cytotoxicity when incubated with U937/Ara-C, as indicated by decreased levels of granzyme B and perforin production, accompanied with less TNF-α and lactate dehydrogenase secretion. In conclusion, AML CDR further evades the anti-tumor immune response which may through MHC molecule and B7 family members.

Mechanism of static loading injury in human skeletal muscle cells.

OBJECTIVE: To establish a cellular-level mechanical injury model for human skeletal muscle cells and investigate changes in the mechanical effect mechanism after such injuries. METHODS: The FX-5000™ Compression System was used to apply constant static mechanical pressure to human skeletal muscle cells. A factorial design analysis was conducted to discover the optimal injury model by evaluating the correlation between the amount of pressure, the duration of mechanical stimulation, and the number of days of observation. Skeletal muscle cell injury was evaluated by measuring cell metabolism, morphology, and calcium homeostasis. RESULTS: Mechanical injury was modeled as continuous pressure of 1 MPa for 2 hours with observation for 3 days. The results show that mechanical injury increased creatine kinase, intracellular Ca2+ concentration, and malondialdehyde content, decreased superoxide dismutase, and caused cell swelling and severe cytoplasmic vacuolization (all P < 0.05). CONCLUSION: This model of mechanically-injured human skeletal muscle cells provides an experimental model for the clinically common skeletal muscle injury caused by static loading pressure. It may be used to study the mechanism of action of treatment methods for mechanically injured skeletal muscle.

Kaempferol efficacy in metabolic diseases: Molecular mechanisms of action in diabetes mellitus, obesity, non-alcoholic fatty liver disease, steatohepatitis, and atherosclerosis.

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases.

Impact of body mass index elevation, Vitamin D receptor polymorphisms and antipsychotics on the risk of Vitamin D deficiency in schizophrenia patients.

Antipsychotics with weight gain as side effect and vitamin D receptor dysfunction associated with single nucleotide polymorphisms (VDR SNPs) may have different effects on vitamin D status. Hence, present study aimed to investigate the relationship between vitamin D with body mass index (BMI), antipsychotics and VDR SNPs (rs2228570, rs1544410, rs7975232 and rs731236) in Malaysian patients with schizophrenia. Serum vitamin D level was measured using competitive enzyme-linked immunosorbent assay kit. VDR SNPs were analyzed using polymerase chain reaction-restriction fragment length polymorphism. We found significantly lower serum vitamin D level in patients with schizophrenia (p < 0.01), especially those taking atypical antipsychotics (p = 0.02) and combined antipsychotics (p = 0.02) and obese (BMI ≥27.5 kg/m2) patients (p = 0.04) after adjustment for covariates. For VDR SNPs, the CT genotype of rs1544410, CA genotype of rs7975232, and AA and AG genotypes of rs731236 may contribute to the significant decreased serum vitamin D level in patients (p < 0.05). Nevertheless, these relationships may differ by populations or medical conditions. The hypotheses of volumetric dilution and sequestration of vitamin D may explain the lower vitamin D level in obese patients. In addition, lifestyle factors such as poor diet and lack of physical activity with less sunlight exposure may cause reduced vitamin D level among patients. As patients in present study were prescribed with various antipsychotics, the effect of each antipsychotic on vitamin D level could not be determined. Thus, future studies should investigate the effect of different types of antipsychotics and obesity on vitamin D level in schizophrenia.

Which countries are ready for a tobacco endgame? A scoping review and cluster analysis.

Various countries have set tobacco endgame targets to eliminate tobacco use by a certain year. Tobacco endgames are generally considered more feasible in countries with advanced tobacco control measures and a smoking prevalence of 15% or less. We conducted a scoping review of 563 articles sourced from news, academic literature, and grey literature to examine global tobacco endgame progress, and grouped 153 countries into clusters based on their tobacco policy implementation score and smoking prevalence to systematically identify countries that might be well positioned to succeed in a tobacco endgame. The EU, Pacific Islands, and 18 other individual countries have set tobacco endgame targets, with another seven countries described as well positioned for an endgame. These were mostly high-income countries with higher smoking prevalence. We identified 28 endgame-ready countries with advanced tobacco policies and a low smoking prevalence. Of these, only five were part of tobacco endgame movements; the remaining 23 were all low-income or middle-income countries in Africa, Latin America, or Asia. Therefore, the global tobacco endgame movement should focus more on low-income and middle-income countries with low smoking rates and advanced tobacco policies, particularly in Africa, Latin America, and Asia.

Effect of Yogurt Intake Frequency on Blood Pressure: A Cross-Sectional Study.

Yogurt consumption is a significant factor in reducing the risk of hypertension and preventing cardiovascular diseases. Although increasing evidence has emerged regarding the potential benefits of probiotics in hypertension, there is a lack of large, cross-sectional studies assessing the association between yogurt intake and blood pressure parameters. We aimed to evaluate the association between yogurt intake frequency and blood pressure. A cross-sectional study was designed using data from the National Health and Nutrition Examination Survey from 2003 to 2004 and 2005 to 2006. We included 3, 068 adults with blood pressure data and yogurt intake data. Multivariate regression analyses revealed significant inverse associations between yogurt and systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and mean arterial pressure (P < 0.05) in nonhypertensive participants (n = 1 822) but not in hypertensive participants (n = 1 246). Furthermore, a high frequency of yogurt intake prevented hypertension; however, no additional antihypertensive effects were observed in patients already diagnosed with hypertension.

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China.

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.

Research Progress of Small Plant Peptides on the Regulation of Plant Growth, Development, and Abiotic Stress.

Small peptides in plants are typically characterized as being shorter than 120 amino acids, with their biologically active variants comprising fewer than 20 amino acids. These peptides are instrumental in regulating plant growth, development, and physiological processes, even at minimal concentrations. They play a critical role in long-distance signal transduction within plants and act as primary responders to a range of stress conditions, including salinity, alkalinity, drought, high temperatures, and cold. This review highlights the crucial roles of various small peptides in plant growth and development, plant resistance to abiotic stress, and their involvement in long-distance transport. Furthermore, it elaborates their roles in the regulation of plant hormone biosynthesis. Special emphasis is given to the functions and mechanisms of small peptides in plants responding to abiotic stress conditions, aiming to provide valuable insights for researchers working on the comprehensive study and practical application of small peptides.

Emergent neural dynamics and geometry for generalization in a transitive inference task.

Relational cognition-the ability to infer relationships that generalize to novel combinations of objects-is fundamental to human and animal intelligence. Despite this importance, it remains unclear how relational cognition is implemented in the brain due in part to a lack of hypotheses and predictions at the levels of collective neural activity and behavior. Here we discovered, analyzed, and experimentally tested neural networks (NNs) that perform transitive inference (TI), a classic relational task (if A > B and B > C, then A > C). We found NNs that (i) generalized perfectly, despite lacking overt transitive structure prior to training, (ii) generalized when the task required working memory (WM), a capacity thought to be essential to inference in the brain, (iii) emergently expressed behaviors long observed in living subjects, in addition to a novel order-dependent behavior, and (iv) expressed different task solutions yielding alternative behavioral and neural predictions. Further, in a large-scale experiment, we found that human subjects performing WM-based TI showed behavior inconsistent with a class of NNs that characteristically expressed an intuitive task solution. These findings provide neural insights into a classical relational ability, with wider implications for how the brain realizes relational cognition.

Prenatal co-exposure to diisodecyl phthalate and ozone contribute to depressive behavior in offspring mice through oxidative stress and TWIST1 participation.

Exposure to diisodecyl phthalate (DIDP) during early pregnancy may be a risk factor for depressive behavior in offspring. While ozone (O3) exposure also raises the probability of depressive behavior during the preceding DIDP-induced process. In the present study, we investigated the effects of prenatal exposure to DIDP and O3 on the development of depressive-like behavior in offspring mice. The study found that prenatal exposure to both DIDP and O3 significantly increased depressive-like behavior in the offspring mice compared to either DIDP or O3 alone. Prenatal exposure to DIDP and O3 obviously increased the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, and decreased the levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissues of offspring mice. Transcriptome analysis further revealed significant alterations in genes related to oxidative stress and TWIST1 (a helix-loop-helix transcription factor) in response to the combined exposure to DIDP and O3. HPA axis activation, dysregulation of neurodevelopmental factors, oxidative stress and TWIST1 involvement, collectively contributed to the development of depression-like behaviors in offspring mice following prenatal exposure to DIDP and O3. Moreover, the study also verified the potential role of oxidative stress using vitamin E as an antioxidant. The findings provide valuable evidence for the relationship between co-exposure to DIDP and O3 and depression, highlighting the importance of considering the combined effects of multiple environmental pollutants in assessing their impact on mental health outcomes.